What if we could indulge in sugary satisfaction without adverse consequences? That’s what artificial sweeteners promise, or at least suggest: you can literally have your cake and eat it too without suffering the metabolic or hormonal repercussions of consuming real sugar.

Sometimes called “non-caloric sweeteners” or “sugar substitutes,” these fake sweetenersare ubiquitous in foods, beverages, medicines, and even mouthwashes. Marketers cleverly position them as healthier or less harmful low-calorie sweetener (or zero-calorie sweetener) options to real sugar. While some researchers argue artificial sweeteners aresafe in small amounts, others question their safety (especially among children). Some experts believe aspartame, sucralose, and other artificial sweeteners are far from the perfect sugar substitute.

Artificial sweeteners “provide greater food choices to people looking to cut down calories and improve the palatability of food,” researchers say. “However, many of their purported beneficial effects remain invalidated in large scale clinical studies, and some recent evidence also questions these previously established benefits.” Regardless, some people have bought into the “free pass” mentality that artificial sweeteners exude. Research shows that in 2008,nearly one in four adults (24.1 percent) consumed a drink containing artificial sweeteners. Critics believe, however, artificial sweeteners are anything but a free ride.

“Rather than accept the fact that we’re eating too much sugar and try to eat less, we look for a magic loophole—an easy way to avoid doing the smart thing,” says Mark Hyman, MD, in Food: What the Heck Should I Eat?. “We saw it with trans fats and margarine, which were created as replacements for butter but turned out to be unsafe for human consumption. And it is happening again with artificial sweeteners.”

How Aspartame, Sucralose, and Other Artificial Sweeteners Emerged

Artificial sweeteners are hardly new. They first appeared in 1879 with saccharin, which isabout 300 times sweeter than sucrose or table sugar, but has a bitter aftertaste. First promoted for people with diabetes, saccharin was later marketed to women who wanted to lose weight during World War 2. Tab®, the first diet soda introduced in 1963, was initially sweetened with saccharin.

Saccharin was later banned because it created bladder tumors in rats. Some critics suggested that it might also cause cancer in humans. However, researchers later noted that you would need to drink the equivalent of 800 12-ounce diet sodas with saccharin daily to get the amount that caused those tumors in rats. Saccharin was eventually acquitted and considered “not hazardous” in America and many other countries.

Today, other artificial sweeteners have replaced saccharin, and altogether theyhave become a big business. Researchersestimated the sugar-substitute market was worth $13.26 billion, in 2015, and could reach a whopping $16.5 billion by 2020. While they appeal to a broad demographic (including people with diabetes), the big sell for artificial sweeteners is for weight loss. Yet interestingly, research shows they can create the opposite effect —they can make you gain weight and contribute to the development of type 2 diabetes.

“Normally, when you eat or drink something sweet, it’s accompanied by lots of calories. But not when you consume artificial sweeteners,” says Hyman. “This confuses your brain. It senses that the taste of sugar without the accompanying calories from glucose and fructose is wrong, and it tries to correct the imbalance by making you hungrier. As a result, you end up eating more food, not less.”

One rodent study found low-calorie sweetenersled the animals to overeat.“Artificial sweeteners, precisely because they are sweet,encourage sugar craving and sugar dependence,” says Yang. In other words, it might be the effects that artificial sweeteners trigger that lead to weight gain. Six artificial sweetenershave been tested and approved by the U.S. Food and Drug Administration (FDA): Acesulfame potassium, aspartame, the aforementioned saccharin, sucralose, neotame, and advantame. (You’ve likely never heard of those last two.)

Acesulfame potassium (sometimes called acesulfame K or ace-K) might sound healthy. After all, it has potassium in its name, and potassium is a healthy mineral, right? Yet one animal study found that ace-K could increase body weight, adversely impact gut health, and trigger inflammation.

Common Artificial Sweeteners & Their Side Effects

Of the six artificial sweeteners the FDA approved, aspartame and sucralose are the two most ubiquitous ones in many soft drinks and foods. Let’s look at each more closely.

Aspartame

Aspartame, an artificial sweetener that first appeared in many food and drink products during the 1980s, earned approval by the FDA in 1981. Sold as NutraSweet® and Equal®, aspartame sounds harmless. Manufacturers make this sweetener byjoining together the amino acids aspartic acid and phenylalanine. For people with the genetic disorder phenylketonuria or other specific health conditions, phenylalanine can create intellectual disabilities, brain damage, seizures,and other problems. Federal regulations require any food or beverage with aspartame to have the warning: “Phenylketonurics: Contains phenylalanine.”

Some organizations including the American Cancer Society argue aspartameis mostly safe. However, some researchers question its safety includingits cancer-causing potential. More recent rodent studies published in peer-reviewed journals show that aspartame can be cancer-causing, leading some researchers toreconsider the safety of this artificial sweetener.

Most studies questioning the safety of aspartame are animal studies. Regardless, research shows that using or over-consuming aspartame cantrigger or exacerbate oxidative stress, damage cells, and contribute to systemic inflammation.Other research suggeststhe side effects of aspartameinclude headaches; depression; Alzheimer’s disease; a risk of preterm delivery; behavioral effects; cardiovascular impact; and risk of chronic kidney disease.

Sucralose

Sucralose, marketed as Splenda® and themost widely used artificial sweetener, is 600 times sweeter than sugar. Sucralose tastes like real sugar, doesn’t have a bitter aftertaste, has a long shelf life, and remains stable at high temperatures, making it ideal for manufacturers to use in various foods and beverages.

Artificial Sweeteners: What’s the Solution?

Ultimately, the impact and side effects of artificial sweeteners on weight and disease risk remain controversial. Some studiesshow adverse effects; others don’t. We don’t have conclusive evidence that artificial sweeteners can be harmful or increase your risk for weight gain and diabetes.

Multiple factors probably contribute here, including how much you use, what other foods you consume, and lifestyle factors including your level of physical activity. Besides, how do you define “safe” regarding these sweeteners? Some experts, like Hyman, argue the only acceptable amount of artificial sweeteners is zero. Real sugar isn’t healthy, but artificial sweeteners might be worse because they give you a zero-calorie “halo effect” to overindulge in processed foods and sweet beverages.

Be aware too that artificial sweeteners hide in places you might not imagine. Any time you see “sugar-free” or “no-sugar-added” on the label of a sweet food (such as ketchup) or beverage, read the ingredients. Chances are it contains aspartame or sucralose. Considering artificial sweeteners’ less-than-flattering reputation, manufacturers look for natural sweetener alternatives that don’t create problems like sugar or artificial sweeteners and potentially offer some health benefits.